The invention is a process for providing high yields of an (R)-hydroxy ester by reducing an alpha-keto ester using a ketoreductase enzyme.
Simon et al., Pure & Appl. Chem., Vol. 64, No. 8, pp. 1181–186, 1992, describes properties and mechanistic aspects of redox enzymes from anaerobes suitable for bioconversions. Kataoka et al., Biochimica et Biophysica Acta 1122 (1992) 57–62, describes an NADPH-dependent aldehyde reductase (EC 1.1.1.2) isolated from red yeast Sporobolomyces salmonicolor AKU 4429, which catalyzes the reductions of D-glucuronate, D-glucose, D-xylose and D-galactose at high concentrations. Kataoka et al., Arch. Microbial. (1992) 157: 279–283, describes distribution and immunological characterization of microbial aldehyde reductases in red yeast Sporobolomyces salmonicolor AKU 4429. Kita et al., Applied and Environmental Microbiology, July 1996, p. 2303–2310, describe cloning of aldehyde reductase gene from red yeast Sporobolomyces salmonicolor AKU 4429, and characterization of the gene and its product.
Yasohara et al., Appl. Microbiol. Biotechnol. (1999) 51: 847–851, describe synthesis of optically active ethyl 4-chloro-3-hydroxybutanoate by microbial reduction using Candida magnoliae. Shimizu et al., Journal of Molecular Catalysis B: Enzymatic 5 (1998) 321–325, describes chiral alcohol synthesis with Sporobolomyces salmonicolor and Candida magnoliae yeast carbonyl reductases. Shimizu et al. Applied and Environmental Microbiology, August 1990 p. 2374–2377, describes stereoselective reduction of ethyl 4-chloro-3-oxobutanoate by a microbial aldehyde reductase in an organic solvent-water diphasic system. Aldehyde reductase isolated from Sporobolomyces salmonicolor AKU 4429 and glucose dehydrogenase were used. Krix et al. Journal of Biotechnology 53 (1997) 29–39 describe enzymatic reduction of alpha-keto acids leading to L-amino acids, D- or L-hydroxy acids. The investigation used leucine dehydrogenase and phenylalanine dehydrogenase isolated from different organisms.
Schummer et al., Tetrahedron Vol. 47, No. 43, pp. 9019–9034, 1991, describes polyfunctional (R)-2-hydroxycarboxylic acids by reduction of 2-oxo acids with hydrogen gas or formate and resting cells of Proteus vulgaris. 